High-speed combinatorial methods often involve the use of array technologies that require accurate dispensing of fluids. In order to carry out combinatorial techniques, numerous fluid dispensing techniques have been explored, such as pin spotting, pipetting, inkjet printing, and acoustic ejection. Acoustic ejection provides a number of advantages over other fluid dispensing technologies. In contrast to inkjet devices, nozzleless fluid ejection devices are not subject to clogging and their associated disadvantages, e.g., misdirected fluid or improperly sized droplets. Furthermore, acoustic technology does not require the use of capillaries or involve invasive mechanical actions, for example, those associated with the introduction of a pipette tip into a reservoir of fluid.
Acoustic ejection has been described in a number of patents and may be used to dispense a plurality of fluids at high speeds and with great accuracy. For example, U.S. Patent Application Publication Ser. No. 20020037579 to Ellson et al. describes a device for acoustically ejecting a plurality of fluid droplets toward discrete sites on a substrate surface for deposition thereon. The device includes an acoustic radiation generator for generating acoustic and a focusing means, e.g., a curved surface, for focusing acoustic radiation generated by the generator. In operation, the acoustic generator is acoustically coupled to the reservoir and activated to generate acoustic radiation. The focusing means then focuses the generated acoustic radiation at a point near a free fluid surface within the fluid contained in the reservoir. As a result, a fluid droplet is ejected from reservoir.
Acoustic radiation may also be used to assess the contents of one or more reservoirs. For example, the device described in U.S. Patent Application Publication No. 20020037579 to Ellson et al. may also be used to produce a detection acoustic wave that is transmitted to the fluid surface of the reservoir to become a reflected acoustic wave. Characteristics of the reflected acoustic radiation may then be analyzed in order to assess the spatial relationship between the acoustic radiation generator and the fluid surface. In addition, pool depth feedback technology using acoustic radiation is described in U.S. Pat. No. 5,520,715 to Oeftering. Furthermore, U.S. Patent Application Publication No. 20020094582 to Williams describes similar acoustic ejection and detection technology. In some instances, detailed information relating to the contents of fluid in reservoirs may be obtained. For example, U.S. Patent Application Publication Nos. 20030101819 and 20030150257, each to Mutz et al., describe devices and methods for acoustically assessing the contents in a plurality of reservoirs.
As discussed above, when acoustic radiation is used to analyze the contents of a reservoir or to eject a fluid droplet therefrom, a generator for generating acoustic radiation is placed in acoustic coupling relationship with the reservoir. Although the generator may be placed within the reservoir to establish acoustic coupling, e.g., submerged in a fluid contained in the reservoir, submersion is undesirable when the acoustic generator is used to eject different fluids in rapid succession. Cleaning would be required to avoid contamination between the fluids. Thus, a preferred approach is to couple the generator to an exterior surface of the reservoir and to avoid placing the generator in the reservoir. As a result, the generator does not contact any fluid that the reservoir may contain.
For example, acoustic coupling may be achieved between an acoustic generator and a reservoir via an acoustic coupling medium. As described in U.S. Patent Application Publication No. 20020037579, such a coupling medium allows transmission of acoustic radiation therethrough and into the reservoir. Preferably, the acoustic coupling medium is an acoustically homogeneous fluid in conformal contact with both acoustic generator and the reservoir.
When a single acoustic radiation generator is used in conjunction with a plurality of reservoirs, the generator may be placed in acoustic coupling relationship in rapid succession to each of the reservoirs via the acoustic coupling fluid. Accordingly, the generator, the reservoirs, or both must be rapidly displaced with respect to each other for high-throughput techniques. Such rapid movement may cause uncontrolled flow of the acoustic coupling fluid. As a result, conformal contact between the acoustic generator and the reservoirs may not be achieved, thereby compromising the performance of the device. In some instances, uncontrolled acoustic fluid flow may result in the contamination of the reservoir contents, presence of sound-reflecting bubbles in the acoustic path, and/or degradation of device components.
Thus, there is a need in the art for improved methods and devices that are capable of high-speed monitoring and or ejection of fluid in a plurality of reservoirs within improved control over the placement and flow of acoustic coupling fluid between an acoustic generator and a reservoir.